Vedavati G. Puranik

Synthesis, Electronic Structure, DNA and Protein Binding, DNA Cleavage, and Anticancer Activity of Fluorophore-Labeled Copper(II) Complexes

Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)](+)(2) and [Cu(nip)2](2+) (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1-3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal while 3 retains its square planar geometry in the lowest excited state. The interaction of complexes with calf-thymus DNA (CT DNA) has been explored by using absorption, emission, thermal denaturation, and viscosity studies, and the intercalating mode of DNA binding has been proposed. The complexes cleave DNA oxidatively without any exogenous additives. The protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using bovine serum albumin (BSA) as model protein. The compounds showed dynamic quenching behavior. Further, the anticancer activity of the complexes on MCF-7 (human breast cancer), HeLa (human cervical cancer), HL-60 (human promyelocytic leukemia), and MCF-12A (normal epithelial) cell lines has been studied. It has been observed that 3 exhibits higher cytotoxicity than 2, and the cells undergo apoptotic cell death.

Valence‐State Analysis through Spectroelectrochemistry in a Series of Quinonoid‐Bridged Diruthenium Complexes [(acac)2Ru(μ‐L)Ru(acac)2]n (n=+2, +1, 0, −1, −2)

The quinonoid ligand-bridged diruthenium compounds [(acac)(2)Ru(mu-L(2-))Ru(acac)(2)] (acac(-)=acetylacetonato=2,4-pentanedionato; L(2-)=2,5-dioxido-1,4-benzoquinone, 1; 3,6-dichloro-2,5-dioxido-1,4-benzoquinone, 2; 5,8-dioxido-1,4-naphthoquinone, 3; 2,3-dichloro-5,8-dioxido-1,4-naphthoquinone, 4; 1,5-dioxido-9,10-anthraquinone, 5; and 1,5-diimido-9,10-anthraquinone, 6) were prepared and characterized analytically. The crystal structure analysis of 5 in the rac configuration reveals two tris(2,4-pentanedionato)ruthenium moieties with an extended anthracenedione-derived bis(ketoenolate) pi-conjugated bridging ligand. The weakly antiferromagnetically coupled {Ru(III)(mu-L(2-))Ru(III)} configuration in 1-6 exhibits complicated overall magnetic and EPR responses. The simultaneous presence of highly redox-active quinonoid-bridging ligands and of two ruthenium centers capable of adopting the oxidation states +2, +3, and +4 creates a large variety of possible oxidation state combinations. Accordingly, the complexes 1-6 exhibit two reversible one-electron oxidation steps and at least two reversible reduction processes. Shifts to positive potentials were observed on introduction of Cl substituents (1-->2, 3-->4) or through replacement of NH by O (6-->5). The ligand-to-metal charge transfer (LMCT) absorptions in the visible region of the neutral molecules become more intense and shifted to lower energies on stepwise reduction with two electrons. On oxidation, the para-substituted systems 1-4 exhibit monocation intermediates with intervalence charge transfer (IVCT) transitions of Ru(III)Ru(IV) mixed-valent species. In contrast, the differently substituted systems 5 and 6 show no such near infrared (NIR) absorption. While the first reduction steps are thus assigned to largely ligand-centered processes, the oxidation appears to involve metal-ligand delocalized molecular orbitals with variable degrees of mixing.

Sequence-Specific Unusual (1→2)-Type Helical Turns in α/β-Hybrid Peptides

This article describes novel conformationally ordered alpha/beta-hybrid peptides consisting of repeating l-proline-anthranilic acid building blocks. These oligomers adopt a compact, right-handed helical architecture determined by the intrinsic conformational preferences of the individual amino acid residues. The striking feature of these oligomers is their ability to display an unusual periodic pseudo beta-turn network of nine-membered hydrogen-bonded rings formed in the forward direction of the sequence by 1-->2 amino acid interactions both in solid-state and in solution. Conformational investigations of several of these oligomers by single-crystal X-ray diffraction, solution-state NMR, and ab initio MO theory suggest that the characteristic steric and dihedral angle restraints exerted by proline are essential for stabilizing the unusual pseudo beta-turn network found in these oligomers. Replacing proline by the conformationally flexible analogue alanine (Ala) or by the conformationally more constrained alpha-amino isobutyric acid (Aib) had an adverse effect on the stabilization of this structural architecture. These findings increase the potential to design novel secondary structure elements profiting from the steric and dihedral angle constraints of the amino acid constituents and help to augment the conformational space available for synthetic oligomer design with diverse backbone structures.

Use of Enantiomerically Pure 7-Azabicyclo[2.2.1]heptan-2-ol as a Chiral Template for the Synthesis of Aminocyclitols

Using enantiopure 7-azabicyclo[2.2.1]heptane-2-ol, the synthesis of cis- as well as trans-2-aminocyclohexanols, dihydroconduramine E-1, and ent-conduramine F-1 has been described.

Dioxomolybdenum(VI) and dioxotungsten(VI) complexes of isomeric ONO donor ligands and the X-ray crystal structure of [MoO2(o-OC6H4CHNCH2C6H4O)(MeOH)]2·MeOH

Abstract Dioxomolybdenum(VI) and dioxotungsten(VI) complexes of two isomeric Schiff bases derived from salicylaldehyde, 2-hydroxy-1-naphthaldehyde and o-hydroxybenzylamine or o-aminobenzylalcohol have been prepared and characterized.1H NMR spectral data confirm the formation of [MO2L] (M = Mo or W, LH2 = ligand) types of complexes except the complex of dioxomolybdenum(VI) with the ligand salicylaldehyde-o-hydroxybenzylamine (H2sal-OHYBA) which forms [MoO2(sal-OHYBA)·CH3OH]. An X-ray study of [MoO2(sal-OHYBA)·CH3OH] shows the presence of distorted octahedral geometry around molybdenum in which the tridentate ligand occupies meridional position where two anionic oxygens are mutuallytrans and arecis to thecis dioxo group. Generally the tungsten complex is more stable to decomposition than the molybdenum one within the same ligand.

A potential plasmid-curing agent, 8-epidiosbulbin E acetate, from Dioscorea bulbifera L. against multidrug-resistant bacteria

Bioassay-guided fractionation of an aqueous methanolic extract of Dioscorea bulbifera L. bulbs was performed using organic solvents. A novel plasmid-curing compound was identified as 8-epidiosbulbin E acetate (EEA) (norditerpene) on the basis of modern spectroscopic analysis and X-ray crystallography. EEA exhibited broad-spectrum plasmid-curing activity against multidrug-resistant (MDR) bacteria, including vancomycin-resistant enterococci. EEA cured antibiotic resistance plasmids (R-plasmids) from clinical isolates of Enterococcus faecalis, Escherichia coli, Shigella sonnei and Pseudomonas aeruginosa with 12-48% curing efficiency. The reference plasmids of Bacillus subtilis (pUB110), E. coli (RP4), P. aeruginosa (RIP64) and Salmonella typhi (R136) were cured with efficiency ranging from 16% to 64%. EEA-mediated R-plasmid curing decreased the minimal inhibitory concentration of antibiotics against MDR bacteria, thus making antibiotic treatment more effective. The antibiotic resistance pattern revealed that the compound was effective in the reversal of bacterial resistance to various antibiotics. In addition, the compound did not show any cytotoxicity against a broad range of human cancer cell lines, namely MCF-7 (breast cancer), SiHa (cervical cancer) and A431 (epidermal carcinoma), and hence has the potential to be used as a lead compound for drug discovery programmes.

Asymmetric synthesis of α-hydroxy acids via β-Lactams

Abstract A diastereoselective synthesis of β-Lactams 5a-e and 6a-e has been achieved, via a Staudinger reaction using imines derived from (1 S )-(+)-camphor-10-sulfonamide, in good yields. The major diastereomers 6a-e were isolated in pure form by crystallization. The absolute configuration of the β-lactam 6b was established as 3 R and 4 S by X-ray analysis. The major diastereomers 6b and 6c were converted into enantiomerically pure α-hydroxy ester derivatives 7–9 .

Monitoring Cellular Uptake and Cytotoxicity of Copper(II) Complex Using a Fluorescent Anthracene Thiosemicarbazone Ligand

The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase.

InCl3‐Mediated Addition of Indole to Isatogens: An Expeditious Synthesis of 13‐deoxy‐Isatisine A

A strategy directed towards the total synthesis of isatisine A that involves several late-stage metal-catalyzed transformations that address the key carbon-carbon and carbon-heteroatom bond formations has been developed. As a part of this strategy, methods for the addition of indoles to isatogens that lead selectively to either 2,2-disubstituted N-hydroxyindolin-3-one or 2,2-disubstituted indolin-3-one compounds have been developed by employing InCl(3) as a catalyst or as the reagent. The present methods provide the first examples of the additions of indoles to the isatogen nucleus. To demonstrate its viability, the synthesis of 13-deoxy-isatisine A has been completed in ten steps from a known and easily available lactone.

Asymmetric synthesis of azetidin-2-ones by [2+2] cycloaddition using chiral imines derived from d-(+)-glucose

Abstract Asymmetric synthesis of β-lactams by the [2+2] cycloaddition of ketenes with chiral imines derived from d -(+)-glucose was carried out; predominantly cis-β-lactams were formed with very high diastereoselectivity. The stereochemistry at C-3 and C-4 was established as 3S and 4R from the known absolute configuration of the sugar moiety.